Serum Proteomic Profiling in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Sinan Wu,1– 4,* Ke Huang,1– 4,* Chenli Chang,1– 5 Xu Chu,1– 4,6 Kun Zhang,7 Baicun Li,1– 4 Ting Yang1– 4 1National Center for Respiratory Medicine, Beijing, People’s Republic of China; 2National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 3Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, People’s Republic of China; 7Biotree-Shanghai, Focus Dream Park, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ting Yang; Baicun Li, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No. 2, East Yinghua Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel [phone], Email [email protected]; [email protected]: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with high morbidity and mortality rates. This study used proteomic profiling of serum to identify the differentially expressed proteins in COPD patients compared with healthy controls, to expand the knowledge of COPD pathogenesis and to ascertain potential new targets for diagnosis and treatment of COPD.Methods: Serum samples were collected from 56 participants (COPD group n = 28; Healthy Control group n = 28). A data-independent acquisition quantitative proteomics approach was used to identify differentially expressed proteins (DEPs) between the two groups. Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment, and protein–protein interaction analyses of DEPs were conducted to identify their relevant biological processes, cellular components, and related pathways. We used a parallel reaction monitoring (PRM)-based targeted quantitative proteomics approach to validate those findings.Results: Of 8484 peptides identified by searching the UniProtKB/Swiss-Prot knowledgebase, 867 proteins were quantifiable, of which 20 were upregulated and 35 were downregulated in the COPD group. GO functional annotation indicated that the subcellular localization of most DEPs was extracellular. The top three molecular functions of the DEPs were signaling receptor binding, antigen binding, and immunoglobulin receptor binding. The most relevant biological process was immune response. The transforming growth factor-β signaling pathway, Staphylococcus aureus infection, and hematopoietic cell lineage were the top three pathways identified in the KEGG pathway functional enrichment. Our PRM analyses confirmed the identification of 11 DEPs identified in our data-independent acquisition analyses, 8 DEPs were upregulated and 3 DEPs were downregulated.Conclusion: This study using data-independent acquisition analyses with PRM confirmation of findings identified 11 DEPs in the serum of patients with COPD. These DEPs are potential diagnostic or prognostic biomarkers or may be future targets for the treatment of COPD.Keywords: chronic obstructive pulmonary disease, proteomics, differentially expressed proteins, data-independent acquisition, parallel reaction monitoring

Keywords

• chronic obstructive pulmonary disease
• proteomics
• differentially expressed proteins
• data-independent acquisition
• parallel reaction monitoring